Any feedback?
Information on EC 1.1.1.286 - isocitrate-homoisocitrate dehydrogenase
for references in articles please use BRENDA:EC1.1.1.286Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
1.1.1.286 isocitrate-homoisocitrate dehydrogenaseIUBMB Comments
Requires Mn2+ and K+ or NH4+ for activity. Unlike EC 1.1.1.41, isocitrate dehydrogenase (NAD+) and EC 1.1.1.87, homoisocitrate dehydrogenase, this enzyme, from Pyrococcus horikoshii, can use both isocitrate and homoisocitrate as substrates. The enzyme may play a role in both the lysine and glutamate biosynthesis pathways.
Specify your search results
The expected taxonomic range for this enzyme is: Archaea, Bacteria, Eukaryota
Reaction Schemes
+
=
+
+
+
Synonyms
saci_2375, isocitrate-homoisocitrate dehydrogenase, 
more
topPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
HICDH
isocitrate-homoisocitrate dehydrogenase
Saci_2375
TK0280
additional information
-
HIcDH is a member of the family of pyridine nucleotide-linked beta-hydroxy acid oxidative decarboxylases
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
(1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate + NAD+ = 2-oxoadipate + CO2 + NADH + H+
-
-
-
-
(1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate + NAD+ = 2-oxoadipate + CO2 + NADH + H+
chemical mechanism on the basis of the pH dependence of kinetic parameters, dissociation constants for competitive inhibitors, and multiple-substrate deuterium/13C isotope effects suggesting a stepwise mechanism with hydride transfer preceding decarboxylation, the decarboxylation step contributes only slightly to rate limitation, overview
-
isocitrate + NAD+ = 2-oxoglutarate + CO2 + NADH + H+
-
-
-
-
isocitrate + NAD+ = 2-oxoglutarate + CO2 + NADH + H+
chemical mechanism on the basis of the pH dependence of kinetic parameters, dissociation constants for competitive inhibitors, and multiple-substrate deuterium/13C isotope effects suggesting a stepwise mechanism with hydride transfer preceding decarboxylation, the decarboxylation step contributes only slightly to rate limitation, overview
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PATHWAY SOURCE
PATHWAYS
BRENDA
KEGG
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SYSTEMATIC NAME
IUBMB Comments
isocitrate(homoisocitrate):NAD+ oxidoreductase (decarboxylating)
Requires Mn2+ and K+ or NH4+ for activity. Unlike EC 1.1.1.41, isocitrate dehydrogenase (NAD+) and EC 1.1.1.87, homoisocitrate dehydrogenase, this enzyme, from Pyrococcus horikoshii, can use both isocitrate and homoisocitrate as substrates. The enzyme may play a role in both the lysine and glutamate biosynthesis pathways.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CAS REGISTRY NUMBER
COMMENTARY
9001-58-5
-
9067-90-7
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate + NAD+
2-oxoadipate + CO2 + NADH + H+
-
chemical mechanism, stereochemistry of hydride transfer to NAD, overview
-
-
?
3-isopropylmalate + NAD+
?
-
at 0.1% of the rate with homoisocitrate
-
-
?
3-isopropylmalate + NAD+
2-oxoisocaproate + CO2 + NADH + H+
-
-
-
?
3-isopropylmalate + NAD+
2-oxoisocaproate + CO2 + NADH + H+
-
-
-
?
homoisocitrate + NAD+
2-oxoadipate + CO2 + NADH + H+
-
-
-
?
homoisocitrate + NAD+
2-oxoadipate + CO2 + NADH + H+
-
-
-
?
homoisocitrate + NAD+
2-oxoadipate + CO2 + NADH + H+
-
-
-
r
homoisocitrate + NAD+
? + NADH
-
1.5fold preferred over isocitrate
-
-
?
homoisocitrate + NADP+
2-oxoadipate + CO2 + NADPH + H+
-
-
-
r
homoisocitrate + NADP+
2-oxoadipate + CO2 + NADPH + H+
-
-
-
r
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH + H+
-
about 20times more efficient than homoisocitrate, NAD+ is preferred over NADP+
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH + H+
-
slow substrate
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH + H+
-
rapid equilibrium random catalytic mechanism, stereochemistry of hydride transfer to NAD, overview
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH + H+
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH + H+
about 20times more efficient than homoisocitrate
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH + H+
-
-
-
r
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH + H+
Thermus thermophilus HB27 / ATCC BAA-163 / DSM 7039
about 20times more efficient than homoisocitrate
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
NAD+ is preferred over NADP+
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
NAD+ is preferred over NADP+
-
-
?
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
r
additional information
?
-
-
the enzyme catalyzes the fourth reaction of the alpha-aminoadipate pathway for lysine biosynthesis, the conversion of homoisocitrate to alpha-ketoadipate using NAD+ as an oxidizing agent
-
-
?
additional information
?
-
Saci_2375 exhibits distinct and similar activities for isocitrate and homoisocitrate, but no detectable activity for 3-isopropylmalate. Saci_2375 is a dual function enzyme serving as isocitrate-homoisocitrate dehydrogenase
-
-
?
additional information
?
-
-
Saci_2375 exhibits distinct and similar activities for isocitrate and homoisocitrate, but no detectable activity for 3-isopropylmalate. Saci_2375 is a dual function enzyme serving as isocitrate-homoisocitrate dehydrogenase
-
-
?
additional information
?
-
Saci_2375 exhibits distinct and similar activities for isocitrate and homoisocitrate, but no detectable activity for 3-isopropylmalate. Saci_2375 is a dual function enzyme serving as isocitrate-homoisocitrate dehydrogenase
-
-
?
additional information
?
-
residues Thr71 and Ser80 play important roles in the recognition of homoisocitrate and isocitrate while the hydrophobic region consisting of Ile82 and Leu83 is responsible for the recognition of 3-isopropylmalate. Importance of a water-mediated hydrogen bond network for the stabilization of the beta3-alpha4 loop, including the Thr71 residue, with respect to the promiscuity of the substrate specificity of TK0280
-
-
?
additional information
?
-
residues Thr71 and Ser80 play important roles in the recognition of homoisocitrate and isocitrate while the hydrophobic region consisting of Ile82 and Leu83 is responsible for the recognition of 3-isopropylmalate. Importance of a water-mediated hydrogen bond network for the stabilization of the beta3-alpha4 loop, including the Thr71 residue, with respect to the promiscuity of the substrate specificity of TK0280
-
-
?
additional information
?
-
in contrast to other homoisicitrate dehydrogenases, the homoisocitrate dehydrogenase from the thermophilic bacterium Thermus thermophilus (TtHICDH) catalyzes the reactions using both homoisocitrate and isocitrate as substrates at similar efficiencies
-
-
?
additional information
?
-
dual substrate specificity for homoisocitrate dehydrogenase
-
-
?
additional information
?
-
in contrast to other homoisicitrate dehydrogenases, the homoisocitrate dehydrogenase from the thermophilic bacterium Thermus thermophilus (TtHICDH) catalyzes the reactions using both homoisocitrate and isocitrate as substrates at similar efficiencies
-
-
?
additional information
?
-
dual substrate specificity for homoisocitrate dehydrogenase
-
-
?
additional information
?
-
Thermus thermophilus HB27 / ATCC BAA-163 / DSM 7039
no substrate: 3-isopropylmalate
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
homoisocitrate + NAD+
2-oxoadipate + CO2 + NADH + H+
-
-
-
?
homoisocitrate + NAD+
2-oxoadipate + CO2 + NADH + H+
-
-
-
?
homoisocitrate + NAD+
2-oxoadipate + CO2 + NADH + H+
-
-
-
r
homoisocitrate + NADP+
2-oxoadipate + CO2 + NADPH + H+
-
-
-
r
homoisocitrate + NADP+
2-oxoadipate + CO2 + NADPH + H+
-
-
-
r
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH + H+
-
-
-
?
isocitrate + NAD+
2-oxoglutarate + CO2 + NADH + H+
-
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
r
isocitrate + NADP+
2-oxoglutarate + CO2 + NADPH + H+
-
-
-
r
additional information
?
-
-
the enzyme catalyzes the fourth reaction of the alpha-aminoadipate pathway for lysine biosynthesis, the conversion of homoisocitrate to alpha-ketoadipate using NAD+ as an oxidizing agent
-
-
?
additional information
?
-
Saci_2375 exhibits distinct and similar activities for isocitrate and homoisocitrate, but no detectable activity for 3-isopropylmalate. Saci_2375 is a dual function enzyme serving as isocitrate-homoisocitrate dehydrogenase
-
-
?
additional information
?
-
-
Saci_2375 exhibits distinct and similar activities for isocitrate and homoisocitrate, but no detectable activity for 3-isopropylmalate. Saci_2375 is a dual function enzyme serving as isocitrate-homoisocitrate dehydrogenase
-
-
?
additional information
?
-
Saci_2375 exhibits distinct and similar activities for isocitrate and homoisocitrate, but no detectable activity for 3-isopropylmalate. Saci_2375 is a dual function enzyme serving as isocitrate-homoisocitrate dehydrogenase
-
-
?
additional information
?
-
in contrast to other homoisicitrate dehydrogenases, the homoisocitrate dehydrogenase from the thermophilic bacterium Thermus thermophilus (TtHICDH) catalyzes the reactions using both homoisocitrate and isocitrate as substrates at similar efficiencies
-
-
?
additional information
?
-
in contrast to other homoisicitrate dehydrogenases, the homoisocitrate dehydrogenase from the thermophilic bacterium Thermus thermophilus (TtHICDH) catalyzes the reactions using both homoisocitrate and isocitrate as substrates at similar efficiencies
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NADH
NADH forms specific contacts with enzyme TtHICDH. The 2'- and 3-OHs of the adenine ribose of NADH form hydrogen bonds with Asp265 conserved among HICDHs, which may serve as a determinant for the preference of HICDH family members for NAD+ to NADP+
NADP+
Saci_2375 is an NADP+-dependent enzyme with the ability to function as ICDH, EC 1.1.1.42, and HICDH, EC 1.1.1.87
NADPH
Saci_2375 is an NADP+-dependent enzyme with the ability to function as ICDH, EC 1.1.1.42, and HICDH, EC 1.1.1.87
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
K+
Mg2+
Mn2+
K+
-
best activator, 200 mM activates by 100%, increases the affinity of enzyme for NAD+ at high pH
Mn2+
-
divalent cation required, Mg2+ is preferred over Mn2+, inhibitory above 1 mM
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3-carboxypropylidenemalate
-
a dead-end inhibitor, competitive versus homoisocitrate
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.05
3-isopropylmalate
pH 8.0, 60°C, recombinant His6-tagged mutant S80A
0.31
3-isopropylmalate
pH 8.0, 60°C, recombinant His6-tagged wild-type enzyme
0.68
3-isopropylmalate
pH 8.0, 60°C, recombinant His6-tagged mutant L81P
0.71
3-isopropylmalate
pH 8.0, 60°C, recombinant His6-tagged mutant T71V
0.0073
homoisocitrate
pH 8.0, 60°C, recombinant His6-tagged wild-type enzyme
0.037
homoisocitrate
pH 8.0, 60°C, recombinant His6-tagged mutant S80A
0.042
homoisocitrate
pH 8.0, 60°C, recombinant His6-tagged mutant L81P
0.17
homoisocitrate
pH 8.0, 60°C, recombinant His6-tagged mutant L83R
0.46
homoisocitrate
pH 8.0, 60°C, recombinant His6-tagged mutant I82N
0.94
homoisocitrate
pH 8.0, 60°C, recombinant His6-tagged mutant T71V
0.014
isocitrate
pH 8.0, 60°C, recombinant His6-tagged wild-type enzyme
0.3
isocitrate
pH 8.0, 60°C, recombinant His6-tagged mutant S80A
0.5
isocitrate
pH 8.0, 60°C, recombinant His6-tagged mutant T71V
0.58
isocitrate
pH 8.0, 60°C, recombinant His6-tagged mutant L83R
1.2
isocitrate
pH 8.0, 60°C, recombinant His6-tagged mutant L81P
2.2
isocitrate
pH 8.0, 60°C, recombinant His6-tagged mutant I82N
0.036
NAD+
pH 8.0, 60°C, recombinant His6-tagged wild-type enzyme, with homoisocitrate
0.1
NAD+
pH 8.0, 60°C, recombinant His6-tagged wild-type enzyme, with isocitrate
0.16
NAD+
pH 8.0, 60°C, recombinant His6-tagged mutant L83R, with homoisocitrate
0.25
NAD+
pH 8.0, 60°C, recombinant His6-tagged mutant T71V, with isocitrate
0.32
NAD+
pH 8.0, 60°C, recombinant His6-tagged mutant L81P, with homoisocitrate
0.6
NAD+
pH 8.0, 60°C, recombinant His6-tagged mutant L81P, with isocitrate
0.62
NAD+
pH 8.0, 60°C, recombinant His6-tagged mutant L83R, with isocitrate
0.64
NAD+
pH 8.0, 60°C, recombinant His6-tagged mutant I82N, with homoisocitrate
0.76
NAD+
pH 8.0, 60°C, recombinant His6-tagged mutant S80A, with isocitrate
0.92
NAD+
pH 8.0, 60°C, recombinant His6-tagged mutant S80A, with homoisocitrate
1
NAD+
pH 8.0, 60°C, recombinant His6-tagged mutant T71V, with 3-isopropylmalate
1.2
NAD+
pH 8.0, 60°C, recombinant His6-tagged mutant S80A, with 3-isopropylmalate
1.3
NAD+
pH 8.0, 60°C, recombinant His6-tagged mutant L81P, with 3-isopropylmalate
1.5
NAD+
pH 8.0, 60°C, recombinant His6-tagged mutant T71V, with homoisocitrate
1.5
NAD+
pH 8.0, 60°C, recombinant His6-tagged wild-type enzyme, with 3-isopropylmalate
1.8
NAD+
pH 8.0, 60°C, recombinant His6-tagged mutant I82N, with isocitrate
additional information
additional information
Michaelis-Menten kinetics
-
additional information
additional information
-
kinetic mechanism, detailed overview
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1.5
3-isopropylmalate
pH 8.0, 60°C, recombinant His6-tagged mutant L81P
2.3
3-isopropylmalate
pH 8.0, 60°C, recombinant His6-tagged mutant S80A
4.8
3-isopropylmalate
pH 8.0, 60°C, recombinant His6-tagged wild-type enzyme
9.4
3-isopropylmalate
pH 8.0, 60°C, recombinant His6-tagged mutant T71V
4.8
homoisocitrate
pH 8.0, 60°C, recombinant His6-tagged mutant T71V
6.9
homoisocitrate
pH 8.0, 60°C, recombinant His6-tagged mutant S80A
13
homoisocitrate
pH 8.0, 60°C, recombinant His6-tagged mutant L81P
17
homoisocitrate
pH 8.0, 60°C, recombinant His6-tagged wild-type enzyme
43
homoisocitrate
pH 8.0, 60°C, recombinant His6-tagged mutant L83R
45
homoisocitrate
pH 8.0, 60°C, recombinant His6-tagged mutant I82N
0.22
isocitrate
pH 8.0, 60°C, recombinant His6-tagged mutant T71V
0.71
isocitrate
pH 8.0, 60°C, recombinant His6-tagged mutant S80A
1
isocitrate
pH 8.0, 60°C, recombinant His6-tagged mutant I82N
1.1
isocitrate
pH 8.0, 60°C, recombinant His6-tagged mutant L81P
5
isocitrate
pH 8.0, 60°C, recombinant His6-tagged wild-type enzyme
6.6
isocitrate
pH 8.0, 60°C, recombinant His6-tagged mutant L83R
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2.2
3-isopropylmalate
pH 8.0, 60°C, recombinant His6-tagged mutant L81P
13
3-isopropylmalate
pH 8.0, 60°C, recombinant His6-tagged mutant T71V
15
3-isopropylmalate
pH 8.0, 60°C, recombinant His6-tagged wild-type enzyme
46
3-isopropylmalate
pH 8.0, 60°C, recombinant His6-tagged mutant S80A
5.3
homoisocitrate
pH 8.0, 60°C, recombinant His6-tagged mutant T71V
98
homoisocitrate
pH 8.0, 60°C, recombinant His6-tagged mutant I82N
190
homoisocitrate
pH 8.0, 60°C, recombinant His6-tagged mutant S80A
250
homoisocitrate
pH 8.0, 60°C, recombinant His6-tagged mutant L83R
310
homoisocitrate
pH 8.0, 60°C, recombinant His6-tagged mutant L81P
2300
homoisocitrate
pH 8.0, 60°C, recombinant His6-tagged wild-type enzyme
0.44
isocitrate
pH 8.0, 60°C, recombinant His6-tagged mutant T71V
0.45
isocitrate
pH 8.0, 60°C, recombinant His6-tagged mutant I82N
0.92
isocitrate
pH 8.0, 60°C, recombinant His6-tagged mutant L81P
2.4
isocitrate
pH 8.0, 60°C, recombinant His6-tagged mutant S80A
11
isocitrate
pH 8.0, 60°C, recombinant His6-tagged mutant L83R
360
isocitrate
pH 8.0, 60°C, recombinant His6-tagged wild-type enzyme
0.56
NAD+
pH 8.0, 60°C, recombinant His6-tagged mutant I82N, with isocitrate
0.88
NAD+
pH 8.0, 60°C, recombinant His6-tagged mutant T71V, with isocitrate
0.93
NAD+
pH 8.0, 60°C, recombinant His6-tagged mutant S80A, with isocitrate
1.2
NAD+
pH 8.0, 60°C, recombinant His6-tagged mutant L81P, with 3-isopropylmalate
1.8
NAD+
pH 8.0, 60°C, recombinant His6-tagged mutant L81P, with isocitrate
1.9
NAD+
pH 8.0, 60°C, recombinant His6-tagged mutant S80A, with 3-isopropylmalate
3.2
NAD+
pH 8.0, 60°C, recombinant His6-tagged mutant T71V, with homoisocitrate
3.2
NAD+
pH 8.0, 60°C, recombinant His6-tagged wild-type enzyme, with 3-isopropylmalate
7.5
NAD+
pH 8.0, 60°C, recombinant His6-tagged mutant S80A, with homoisocitrate
9.4
NAD+
pH 8.0, 60°C, recombinant His6-tagged mutant T71V, with 3-isopropylmalate
11
NAD+
pH 8.0, 60°C, recombinant His6-tagged mutant L83R, with isocitrate
41
NAD+
pH 8.0, 60°C, recombinant His6-tagged mutant L81P, with homoisocitrate
50
NAD+
pH 8.0, 60°C, recombinant His6-tagged wild-type enzyme, with isocitrate
70
NAD+
pH 8.0, 60°C, recombinant His6-tagged mutant I82N, with homoisocitrate
270
NAD+
pH 8.0, 60°C, recombinant His6-tagged mutant L83R, with homoisocitrate
470
NAD+
pH 8.0, 60°C, recombinant His6-tagged wild-type enzyme, with homoisocitrate
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.043
3-carboxypropylidenemalate
-
pH 8.0, 25°C, versus homoisocitrate
Please wait a moment until the data is sorted. This message will disappear when t